Hepatitis C treatment highly effective in harder-to-treat people with HIV co-infection, Spanish real-life study shows

Hepatitis C virus (HCV) treatment using direct-acting antivirals (DAAs) is highly effective and safe in harder-to-treat people with HIV co-infection, Spanish researchers report in AIDS. A sustained virological response (SVR), or cure, was observed in 93% of people and only 0.4% stopped treatment because of adverse events. The large proportion of people had advanced fibrosis or had taken a previous course of HCV therapy. Liver cirrhosis/liver stiffness were the only factors associated with treatment failure and use of ribavirin increased the risk of side-effects.

Nevertheless, 87.5% of people with cirrhosis achieved an SVR and no one with cirrhosis who completed a 24-week course of treatment and underwent follow-up testing failed to be cured of hepatitis C. The study findings are highly encouraging for people with co-infection with advanced liver disease – in the past considered harder to treat – the study investigators conclude.

“The present work considered a heterogeneous, unselected cohort of coinfected patients who were treated for their HCV infection under normal clinical practice conditions, and contrasts well with highly-selective randomized clinical trials which do not always equate well to real-life settings,” write the investigators.

“The real-life results of studies performed in developed countries implementing all-oral DAA based regimens in cohorts principally including difficult-to-treat patients (HIV coinfected, cirrhotic, and/or with previous therapy failures), confirm these results.”

Approximately a third of HIV-positive people in Spain have co-infection with HCV. Liver disease caused by HCV is a leading cause of serious illness and death in people with co-infection. In recent years, HCV therapy using all-oral DAA regimens has been developed. In clinical trials, these combinations have achieved SVR rates in excess of 90%. However, there is relatively little data about the efficacy and safety of DAA combinations in people with HIV/HCV co-infection with characteristics usually associated with poorer treatment outcomes, especially more advanced liver disease or therapeutic failure using older regimens.

Investigators in eastern Spain therefore analysed outcomes in 515 people with co-infection who started an all-oral DAA regimen in 2015. Retrospective data were obtained on the proportion of people attaining an SVR 12 weeks after completing a 12 or 24-week course of therapy, and also the proportion of people experiencing adverse events. The investigators also conducted a series of analyses to see if specific patient or treatment factors were associated with the success of therapy or a greater risk of side-effects.

A total of 13 treatment centres in the region close to Valencia participated in the study. The participants had a median age of 50 years and 78% were male. Most (84%) had injecting drug use as their most likely mode of HCV infection. The most common HCV genotype was 1a (47%), with 20% carrying genotype 4 and 14% genotype 1b and 13% genotype 3. Just over half (54%) had cirrhosis, which was diagnosed using elastography (FibroScan, an assessment of liver stiffness) in 95% of people. Just under half (46%) had taken a previous unsuccessful course of HCV therapy based on pegylated interferon or first-generation DAAs.

As regards HIV infection, 95% of individuals were taking antiretroviral therapy (ART) and 90% had a viral load below 50 copies/ml. Median CD4 cell count was 585 cells/mm³. To avoid potential drug interactions, a third of participants modified their ART before staring DAA therapy. The new combinations were mostly based on an integrase inhibitor.

The most widely used DAA regimen was ledipasvir/sofosbuvir (57%). Just over a third of people (37%) were treated with a ribavirin-containing regimen and 7% took a 24-week course of therapy.

Overall, 93% of people had an SVR 12 weeks after the completion of therapy. There was little evidence that outcomes were influenced by baseline characteristics such as age and sex, HCV viral load or previous use of HCV therapy.

The only factors associated with reduced chances of attaining SVR were cirrhosis (p = 0.001) and liver stiffness above 21kPa (p = 0.001).

Only two people (0.4%) stopped treatment because of adverse events, one because of decompensated cirrhosis, the other due to newly diagnosed high-grade lymphoma. Overall, 37% of people reported any adverse events. These were mild in the majority of cases. Adverse events were reported by 54% of the ribavirin-treated patients, with 27% requiring dose reduction.

The investigators’ analyses failed to identify any significant association between specific DAA regimens and the risk of adverse events. However, ribavirin was associated with a nearly three-fold increased risk of side-effects.

“In real-life conditions, difficult-to-treated HIV/HCV-coinfected patients treated with all-oral DAA combinations reach high rates of SVR₁₂, similar to those achieved by monoinfected patients in such conditions,” conclude the authors.

“Future drugs should be focused on reducing the risk of drug-drug interactions, along with an improvement in efficacy in patients with increased liver stiffness.”